The visual system has been relatively neglected in recent multiple sclerosis (MS) research and often it is not even examined in autopsied patients. We propose to study demyelination of the optic nerve clinically and experimentally. We will determine the leukocyte antigens HL-A in idiopathic optic neuritis (ON) and MS patients since the histocompatibility immune system may be linked to the genetic control of susceptibility to disease. We hope to develop a test diagnostic for demyelination through studies of the demyelinating activity of lymphocytes, serum and cerebrospinal fluid (CSF) in in vivo and in in vitro model systems. We plan to study in detail the histopathology of the optic nerve lesion in experimental allergic ON: a new in vivo model of intraocular demyelination in the rabbit produced in our laboratory by the passive transfer of autologous lymphocytes sensitized to myelin basic protein. We will test the feasibility of using the rabbit eye chamber technique to study cells in patients with MS, ON and other diseases and their potential to produce demyelination of intraocular CNS myelin and clinical signs of ON. We will use a new in vivo model system, the optic nerves of Xenopus tadpoles, to determine the demyelinating activity of unconcentrated CSF from patients with MS or ON.